One strategy for controlling tumors is to administer agents that alkylate cellular structures. Procarbazine, streptozotocin, and dacarbazine are examples of antineoplastic agents of this type.
Our co-owned U.S. Pat. Nos. (4,684,747; 4,849,563; and 4,892,887) disclose certain antineoplastic hydrazines with alkylating ability. Specifically, our '747 and '887 Patents disclose N,N'-bis(sulfonyl)hydrazines having methyl or chloroethyl substituents on the hydrazine moiety, as contrasted with N,N'-bis(sulfonyl)hydrazines having no alkyl substituent on the hydrazine moiety. The methyl or chloroethyl substituent is said to be essential for the generation of the reactive species necessary for antineoplastic activity.
We have published other studies on alkylating N,N'-bis(sulfonyl)hydrazines. See, Shyam et al. (1985) J. Med. Chem. 28:525-527; Shyam et al. (1986) J. Med. Chem. 29:1323-1325; Shyam et al. (1987) J. Med. Chem. 30:2157-2161; Penketh et al. (1990) J. Med. Chem. 33:730-732. In particular, Shyam et al. J. Med. Chem. (1990) 33:2259-2264 disclose certain tris(sulfonyl)hydrazines having antineoplastic activity. Specifically, 1-(2-chloroethyl)-1,2,2-tris(methylsulfonyl)hydrazine displays potent antineoplastic activity. 1-Methyl-1,2,2-tris(methylsulfonyl)hydrazine also showed antineoplastic activity and was relatively less toxic.